To date, the association between sleep duration or sleep quality and hyperuricemia has remained unclear. In addition, sleep duration and quality were not considered concomitantly in previous studies. Thus, this study was aimed toward an examination of the association of sleep duration and quality with uric acid level in a Taiwanese population.
A total of 4,555 patients aged ≥18 years were enrolled in this study. The sleep duration was classified into three groups: short (<7 h), normal (7–9 h), and long (≥9 h). The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and poor sleep quality was defined as a global PSQI score of >5.
Poor sleepers were younger and had lower body mass index, blood pressure, uric acid, blood sugar, cholesterol, creatinine level, shorter sleep duration, and engaged in less exercise but had a higher white blood cell count and prevalence of smoking as compared to good sleepers. There were also differences in body mass index, blood pressure, uric acid, blood sugar, lipid profiles, and sleep quality among subjects with different sleep durations. After adjusting for other variables, poor sleep quality was associated with lower uric acid levels. In addition, short sleep duration was positively associated with higher uric acid levels.
Citation: Chou Y-T, Li C-H, Shen W-C, Yang Y-C, Lu F-H, Wu J-S, et al. (2020) Association of sleep quality and sleep duration with serum uric acid levels in adults. PLoS ONE 15(9): e0239185. https://doi.org/10.1371/journal.pone.0239185
Editor: Xianwu Cheng, Nagoya University, JAPAN
Received: May 14, 2020; Accepted: September 1, 2020; Published: September 17, 2020
Copyright: © 2020 Chou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the Supporting Information files.
Funding: This research was funded by the National Cheng Kung University Hospital, Taiwan (NCKUH-10903022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Hyperuricemia is one of most common metabolic disorders in modern society. Its prevalence is approximately 20% worldwide , and it may result in several crystal deposition-related disorders, such as gout, urate nephropathy, and urolithiasis . Furthermore, hyperuricemia is also related to specific medical conditions, such as chronic kidney disease [3, 4], cardiovascular disease [5, 6], hypertension [7, 8], and early mortality . In addition, some studies have demonstrated that high-normal levels of serum uric acid are also associated with risk of diabetes , impaired renal function  and even mild cognitive impairment . However, low uric acid levels have been shown to be related to a higher prevalence of Alzheimer’s disease, Parkinson’s disease (PD), and PD-related diseases such as multiple system atrophy and progressive supra-nuclear palsy [13–16]. Some studies have shown the beneficial aspects of uric acid for its antioxidative and neuroprotective effects [17–21], and the optimal uric acid level appears to be beneficial for health .
Sleep plays an important role in the maintenance of personal health. However, poor sleep quality and sleep deprivation are common nowadays . Various studies have demonstrated that inadequate sleep, such as short sleep duration or poor sleep quality, are associated with cardiovascular disease, obesity, hypertension, non-alcoholic liver disease, diabetes mellitus (DM), dyslipidemia, and even all-cause mortality [23–31].
Physiologically, sleep mediates the level of catecholamine and cortisol [32, 33], which may potentially influence uric acid levels . Most previous studies have found that sleep-disordered breathing such as obstructive sleep apnea (OSA) is associated with hyperuricemia and gout [35–38]. However, studies investigating the relationship between sleep quality or sleep duration and uric acid levels are limited [39–44]. One study found lower serum uric acid levels to be associated with poorer sleep quality . Another study showed that participants had a positive association between sleep quality and uric acid level after acute ischemic stroke . As for the relationship between sleep duration and uric acid, two studies demonstrated that sleep duration was inversely associated with serum uric acids [41, 42], and another study found that long sleepers had a lower prevalence of hyperuricemia . However, the relationship between sleep duration and uric acid was insignificant in another study based on the National Health and Nutrition Examination Survey (NHANES) database . To our knowledge, there have been no studies considering the concomitant influence of both sleep quality and sleep duration on uric acid levels. Thus, this study was aimed toward an evaluation of the association of sleep duration and sleep quality with uric acid levels in an adult population.
A total of 4,592 patients who visited a health center for a self-motivated general health assessment were recruited in this study. Data were obtained from a health examination center at National Cheng Kung University Hospital, from October 2001 to August 2009. Secondary data without any personal identifiable information was used, and the study was approved by the Institutional Review Board of NCKUH in Taiwan (IRB number: A-ER-107-285). Participants aged <18 years, on medications for hyperuricemia, hypertension, DM or dyslipidemia, and those with incomplete data were excluded.
The baseline data included demographic information, personal medical and medication history, lifestyle habits (alcohol consumption, cigarette smoking, and regular exercise), and sleep status. Current alcohol consumption was defined as at least one alcoholic drink per week in the past 6 months. Current smoking was defined as at least 20 cigarettes per month in the past 6 months. Regular exercise was defined as a habit of engaging in vigorous exercise at least 3 times per week. Sleep duration and quality were assessed using the Chinese version of the PSQI , which was used to evaluate the participants’ sleep quality over a 1-month time interval using a self-rated questionnaire. The Chinese version of the PSQI was validated as an assessment tool for evaluating sleep condition, with an overall reliability coefficient of 0.82–0.83, and good test-retest reliability, with a coefficient of 0.85. A Chinese version of the PSQI global score > 5 had a diagnostic sensitivity of 98% and specificity of 55% in terms of distinguishing poor and good sleepers . The PSQI reflects seven important aspect of sleep, including sleep duration, habitual sleep efficiency, sleep latency, subjective sleep quality, use of sleep medications, sleep disturbances, and presence of daytime dysfunction. The total global PSQI scores range from 0 to 21 points, where a lower global PSQI score indicates better sleep quality. Participants with a global PSQI score of >5 were defined as poor sleepers. Sleep duration was categorized into three groups: short (<7 h/day), normal (7–9 h/day), and long (≧9 h/day) .
Each participant’s body weight and height were measured in light indoor clothing. The body mass index (BMI) was calculated as weight (kg)/height squared (m2). Obesity was defined as BMI ≥ 27kg/m2 according to the guidelines suggested by the Department of Health in Taiwan . After resting for at least 5 min, the blood pressure of the right branchial artery of each participant was measured in the supine position. Hypertension was defined as a right brachial systolic blood pressure (SBP) of ≥140 mmHg, a diastolic blood pressure (DBP) ≥ 90 mmHg , or a positive history of hypertension.
After fasting for at least 12 h, all participants underwent blood sampling for basic biochemical examinations. All of the blood samples were drawn from 7 am to 9 am in the morning. None of the women were pregnant when tested. Laboratory data including serum uric acid, FPG, HbA1C, 2-hPG, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), white blood cell (WBC) count, and creatinine levels were collected. For all participants without a medical history of diabetes, a 75-g oral glucose tolerance test was performed after overnight fasting for 12 h, with a normal diet for 3 days before the test and abstaining from smoking for more than one day. DM was defined as a self-reported DM history, 2-h postprandial glucose (2-hPG) of ≧200 mg/dL, fasting plasma glucose (FPG) of ≧126 mg/dL, or hemoglobin A1c (HbA1c) of ≧6.5% according to the American Diabetes Association’s diagnostic criteria . The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation .
The data analysis was performed using SPSS software (version 17.0, SPSS, Inc., Chicago, IL). In the univariate analysis, an independent t-test was performed for the continuous variables and a Pearson’s chi-square analysis was used for the categorical variables to compare the participants’ data based on sleep quality. Sleep durations was categorized into three groups, and a Pearson’s chi-square analysis and an analysis of variance were used, where appropriate. In the multivariate analysis, linear regressions were performed to investigate the association of sleep status, including sleep quality and duration, with uric acid levels. Adjusted variables included age, gender, obesity, estimated glomerular filtration rate (eGFR) <60, TC/HDL-C ratio, WBC count, DM, HTN, current smoking, alcohol consumption, and regular exercise. Statistical significance was defined as p < 0.05.
Of all 4,592 participants recruited for the final analysis, 59.9% were poor sleepers. Table 1 shows a comparison of the participants’ clinical characteristics based on sleep quality. There were significant differences between the good and poor sleepers in terms of age, gender, BMI, blood pressure, uric acid, FPG, TC, WBC count, and renal functions. Poor sleepers had shorter sleep duration, engaged in less exercise, and had a higher prevalence of current smoking. Table 2 shows a comparison of the participants’ clinical characteristics based on sleep duration. There were differences in body mass index, diastolic blood pressure, renal function, uric acid, lipid profiles, and sleep quality scores. The prevalence of poor sleepers, smoking, and exercise habits were also different among subjects with different sleep duration.
During the linear regression analysis, we initially investigated the relationships between uric acid levels and sleep quality and duration, separately. The results revealed that poor sleep quality was associated with lower uric acid levels, whereas short sleep duration was related to higher uric acid levels. Subsequently, we analyzed the relationships between both sleep quality and duration and uric acid levels using a multiple linear regression model. As shown in Table 3, when adjusted for sleep duration, poor sleepers remained associated with lower uric acid levels [b-coefficient: -0.085, 95% confidence interval (CI): −0.161 to −0.008, p = 0.030], and short sleep duration was associated with higher serum uric acid levels (b-coefficient: 0.106, 95% CI: 0.031–0.181, p = 0.006). However, no association was found between long sleeper duration and uric acid levels. In addition, uric acid levels were positively associated with overweight and obesity, the TC/HDL-C ratio, WBC count, hypertension, and alcohol consumption habits, but decreased eGFR levels. In addition, age, DM, and smoking were negatively associated with uric acid levels. In the linear regression model, we observed no multicollinearity among the covariates, with a variance inflation factor < 1.4.
In this study, poor sleep quality was related to lower uric acid levels, and short sleep duration was associated with a higher uric acid levels after adjusting for confounders. To the best of our knowledge, this is the first study that concomitantly investigated the association of both sleep quality and sleep duration with uric acid levels. There have been several studies discussing sleep quality and uric acid levels, but sleep duration was not taken into consideration [39, 40, 44, 51]. One case-control study showed that uric acid levels were negatively related to PSQI scores, indicating reduced uric acid levels in subjects with poor sleep quality . Another study conducted with ischemic stroke patients also showed reduced uric acid levels in individuals with poor sleep quality . However, one study, based on the National Health and Nutrition Examination Survey (NHANES) showed that sleep quality, as analyzed by the Sleep Disorders Questionnaire, was not associated with uric acid levels . The discrepancies in the observed relationships between sleep quality and uric acid levels described in these studies may be related to the differences in population ethnicities, definition of sleep quality, and other potentially adjusting confounders, such as medications for chronic diseases, including diabetes, hypertension, dyslipidemia, and hyperuricemia. In the present study, the population was free from the influence of important cardiometabolic medications, and we concurrently considered the influences of both sleep quality and duration, while carefully adjusting for important confounders. As a result, we found that poor sleep quality was associated with lower uric acid levels.
The possible mechanism for the relationship between sleep quality and uric acid remains unclear. Since sleep disturbances are related to increased systemic inflammation and oxidative stress , the beneficial aspects of uric acid may play a role among good sleepers. Uric acids have been to have antioxidative and neuroprotective effects [14, 17, 19, 21, 52]. A study conducted by Bowman et. al showed that uric acid is an important endogenous antioxidant in the central nervous system . One Korean study revealed that higher uric acids were related to better antioxidative capacity . Previous studies also elucidated that poor sleep is related to increased oxidative stress in both animal and human models [55, 56]. In addition, higher oxidative stress accompanied by poor sleep may cause a greater antioxidative reaction  between uric acid and reactive oxygen species, such as reactions with peroxynitrite or chelation of metal ions [17, 57]. These reactions may cause consumption of uric acid as an anti-oxidant, which may in turn result in lower uric acid levels among poor sleepers .
In terms of sleep duration, the results of this study showed that short duration sleepers had higher uric acid levels. Our results were similar to other studies demonstrating an association between short sleep duration and hyperuricemia [41, 42, 44]. The association between short sleep duration and hyperuricemia may be caused by cardiometabolic disorders since studies have shown that short sleep duration increases the risks associated of obesity, metabolic syndrome, and hypertension [58–60], which are all common risk factors for hyperuricemia. Although we adjusted for obesity, TC/HDL-C ratio, WBC count, DM, and HTN, short sleep duration remained associated with hyperuricemia. Thus, further potential mechanisms for this relationship must be clarified. The literature has shown that sleep loss is associated with elevated catecholamine levels , which may result in increased nucleotide turnover and enhanced production of endogenous uric acid . Furthermore, uric acids act as antioxidants, especially in a hydrophilic environment . However, obesity and metabolic syndrome have shown to be associated with a more hydrophobic environment, which is rich in lipids, resulting in an unfavorable status for the antioxidative effects of uric acid [17, 52]. Thus, uric acid may be relatively limited in its role as an antioxidant and thus may be less likely to be metabolized, resulting in elevated uric acid levels among subjects with short sleep durations.
Our study also found an insignificant relationship between long sleep duration and uric acid levels, when considering sleep quality and other confounding factors. A study based on data from NHANES, from 2005–2006 and 2007–2008, showed no association between long sleep duration and hyperuricemia, whereas a study performed examining an elderly Mediterranean population at high cardiovascular risk revealed that long sleepers had lower uric acid levels [41, 44]. Therefore, the association between long sleep duration and uric acid level remains inconclusive. The inconsistent results between this study and two other studies [33, 36] may be related to subject selection, such as differences in age, race, inclusion criteria, and covariate adjustments. In addition, the sample size of patients with long sleep duration was relatively small in this study (n = 19) and in another study examining an elderly Mediterranean population (n = 37) . Further studies with larger sample sizes are necessary to clarify the relationship between long sleep duration and uric acid levels.
In this study, the serum uric acid level was also positively related to male gender, BMI, hypertension, lipid profile, decreased eGFR, WBC count and alcohol consumption. These results were consistent with those of previous studies [62, 63]. It is well known that males have higher uric acid level than females . Obesity, dyslipidemia, hypertension, and renal insufficiency result in decreased renal excretion of urate and thus cause increased serum uric acid levels . In addition, obesity, and dyslipidemia also affect uric acid levels through elevated insulin resistance and increased urate production [65, 66]. Also, obesity is related to increased visceral fat accumulation, which may result in increased plasma free fatty acids in hepatic tissue and subsequently lead to elevated uric acid production . Higher WBC counts provoke production of tumor necrosis factor-alpha and interleukin-6, which may lead to impaired insulin sensitivity and in turn to higher uric acid levels [68, 69]. As for the negative association between current smoking and uric acid levels, our findings were compatible with those of previous studies. The possible mechanism for this may be (1) inhibition of xanthine oxidase by cyanide during cigarette smoking and (2) increased oxidative stress during tobacco consumption, which results in the depletion of uric acid due to its antioxidative effects [70, 71]. A negative association between uric acid level and diabetes was also observed in this study, which was similar to the findings of a study conducted by Bandaru et al. This inverse relationship may be related to decreased uric acid resorption in the proximal tubule under hyperglycemic status in participants with diabetes . Our study also revealed that uric acid level is inversely related to age. Another study from Chiou et al. showed the same result in a Taiwanese population , which found the youngest male group had the highest uric acid level. The opposite association between age and uric acid may be related to lifestyle change, such as dietary and exercise habits, as well as a rapid increase in the prevalence of obesity and overweight among the younger generation in Taiwan .
Despite the strength of considering sleep duration, sleep quality, and other important covariates of hyperuricemia concomitantly, some limitations still exist in the present study. First, clarifying the causal relationship between sleep status and uric acid levels is difficult under a cross-sectional design. Second, participants with OSA, which is associated with hyperuricemia and gout [35, 37], was excluded only by self-reported history, due to the unavailability of subjective measurements such as polysomnography, and therefore, its influence may have been underestimated. Third, our participants’ sleep quality and duration were obtained from self-reported questionnaires but not measured using objective medical devices, such as polysomnography or sleep actigraphy. Fourth, the sample size of long sleepers was relatively small, and the relationship between long sleep duration and uric acid levels was underestimated. Fifth, the effects of sleep quality on uric acid were relatively small, but significant, in the present study. These results provide a research direction for further studies exploring the association between sleep and uric acid to clarify their relationship. Finally, socioeconomic status  and dietary habits were not examined in this study.
In conclusion, poor sleep quality was found to be related to lower uric acid levels, whereas short sleep duration was associated with higher uric acid levels. The relationship between long sleep duration and uric acid was, however, insignificant.
We are grateful to Prof. Chung-Yi Li for providing statistical consulting services from the Biostatistics Consulting Center, Clinical Medicine Research Center, National Cheng Kung University Hospital. The authors thank Enago (https://www.enago.tw/) for assistance with editing the manuscript. We also thank Savana Moore (Foreign Language Center, College of Liberal Arts, National Cheng Kung University) for the assistance of proofreading the revised manuscript.
- 1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis and rheumatism. 2011;63(10):3136–41. Epub 2011/07/30. pmid:21800283.
- 2. Roughley MJ, Belcher J, Mallen CD, Roddy E. Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies. Arthritis research & therapy. 2015;17:90. Epub 2015/04/19. pmid:25889144; PubMed Central PMCID: PMC4404569.
- 3. Viazzi F, Leoncini G, Ratto E, Pontremoli R. Hyperuricemia and renal risk. High blood pressure & cardiovascular prevention: the official journal of the Italian Society of Hypertension. 2014;21(3):189–94. Epub 2014/02/01. pmid:24482065.
- 4. Sattui SE, Singh JA, Gaffo AL. Comorbidities in patients with crystal diseases and hyperuricemia. Rheumatic diseases clinics of North America. 2014;40(2):251–78. Epub 2014/04/08. pmid:24703346; PubMed Central PMCID: PMC4159668.
- 5. Fu S, Luo L, Ye P, Xiao W. Epidemiological associations between hyperuricemia and cardiometabolic risk factors: a comprehensive study from Chinese community. BMC cardiovascular disorders. 2015;15:129. Epub 2015/10/18. pmid:26475463; PubMed Central PMCID: PMC4608157.
- 6. Borghi C, Verardi FM, Pareo I, Bentivenga C, Cicero AF. Hyperuricemia and cardiovascular disease risk. Expert review of cardiovascular therapy. 2014;12(10):1219–25. Epub 2014/09/07. pmid:25192804.
- 7. Noone DG, Marks SD. Hyperuricemia is associated with hypertension, obesity, and albuminuria in children with chronic kidney disease. The Journal of pediatrics. 2013;162(1):128–32. Epub 2012/07/20. pmid:22809658.
- 8. Karis E, Crittenden DB, Pillinger MH. Hyperuricemia, gout, and related comorbidities: cause and effect on a two-way street. Southern medical journal. 2014;107(4):235–41. Epub 2014/06/18. pmid:24937517.
- 9. Juraschek SP, Tunstall-Pedoe H, Woodward M. Serum uric acid and the risk of mortality during 23 years follow-up in the Scottish Heart Health Extended Cohort Study. Atherosclerosis. 2014;233(2):623–9. Epub 2014/02/19. pmid:24534458.
- 10. Shani M, Vinker S, Dinour D, Leiba M, Twig G, Holtzman EJ, et al. High Normal Uric Acid Levels Are Associated with an Increased Risk of Diabetes in Lean, Normoglycemic Healthy Women. The Journal of clinical endocrinology and metabolism. 2016;101(10):3772–8. Epub 2016/08/18. pmid:27533308.
- 11. Ficociello LH, Rosolowsky ET, Niewczas MA, Maselli NJ, Weinberg JM, Aschengrau A, et al. High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes care. 2010;33(6):1337–43. Epub 2010/03/25. pmid:20332356; PubMed Central PMCID: PMC2875450.
- 12. Schretlen DJ, Inscore AB, Jinnah HA, Rao V, Gordon B, Pearlson GD. Serum uric acid and cognitive function in community-dwelling older adults. Neuropsychology. 2007;21(1):136–40. Epub 2007/01/05. pmid:17201536.
- 13. Shen L, Ji HF. Low uric acid levels in patients with Parkinson's disease: evidence from meta-analysis. BMJ open. 2013;3(11):e003620. Epub 2013/11/20. pmid:24247326; PubMed Central PMCID: PMC3840343.
- 14. Sakuta H, Suzuki K, Miyamoto T, Miyamoto M, Numao A, Fujita H, et al. Serum uric acid levels in Parkinson's disease and related disorders. Brain and behavior. 2017;7(1):e00598. Epub 2017/01/28. pmid:28127516; PubMed Central PMCID: PMC5256181.
- 15. Chen X, Guo X, Huang R, Chen Y, Zheng Z, Shang H. Serum uric acid levels in patients with Alzheimer's disease: a meta-analysis. PLoS One. 2014;9(4):e94084. Epub 2014/04/10. pmid:24714617; PubMed Central PMCID: PMC3979756.
- 16. Pan M, Gao H, Long L, Xu Y, Liu M, Zou J, et al. Serum uric acid in patients with Parkinson's disease and vascular parkinsonism: a cross-sectional study. Neuroimmunomodulation. 2013;20(1):19–28. Epub 2012/11/17. pmid:23154271.
- 17. Sautin YY, Johnson RJ. Uric acid: the oxidant-antioxidant paradox. Nucleosides, nucleotides & nucleic acids. 2008;27(6):608–19. Epub 2008/07/05. pmid:18600514; PubMed Central PMCID: PMC2895915.
- 18. El Ridi R, Tallima H. Physiological functions and pathogenic potential of uric acid: A review. Journal of Advanced Research. 2017. pmid:28748115
- 19. Alvarez-Lario B, Macarron-Vicente J. Is there anything good in uric acid? QJM. 2011;104(12):1015–24. Epub 2011/09/13. pmid:21908382.
- 20. Alvarez-Lario B, Macarron-Vicente J. Uric acid and evolution. Rheumatology (Oxford). 2010;49(11):2010–5. Epub 2010/07/16. pmid:20627967.
- 21. Cutler RG, Camandola S, Malott KF, Edelhauser MA, Mattson MP. The Role of Uric Acid and Methyl Derivatives in the Prevention of Age-Related Neurodegenerative Disorders. Current topics in medicinal chemistry. 2015;15(21):2233–8. Epub 2015/06/11. pmid:26059354.
- 22. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep medicine reviews. 2002;6(2):97–111. Epub 2003/01/18. pmid:12531146.
- 23. Okubo N, Matsuzaka M, Takahashi I, Sawada K, Sato S, Akimoto N, et al. Relationship between self-reported sleep quality and metabolic syndrome in general population. BMC public health. 2014;14:562. Epub 2014/06/07. pmid:24903537; PubMed Central PMCID: PMC4087247.
- 24. Ghorbani A, Esmailzadehha N, Mohammadpoorasl A, Ziaee A. Association of Sleep Quality and Waking Time with Prediabetes: The Qazvin Metabolic Diseases Study, Iran. Sleep Disord. 2015;2015:480742. pmid:26351585; PubMed Central PMCID: PMC4553331.
- 25. Watanabe M, Kikuchi H, Tanaka K, Takahashi M. Association of short sleep duration with weight gain and obesity at 1-year follow-up: a large-scale prospective study. Sleep. 2010;33(2):161–7. Epub 2010/02/24. pmid:20175399; PubMed Central PMCID: PMC2817903.
- 26. Brocato J, Wu F, Chen Y, Shamy M, Alghamdi MA, Khoder MI, et al. Association between sleeping hours and cardiometabolic risk factors for metabolic syndrome in a Saudi Arabian population. BMJ open. 2015;5(11):e008590. pmid:26621514; PubMed Central PMCID: PMC4679834.
- 27. Arora T, Jiang CQ, Thomas GN, Lam KB, Zhang WS, Cheng KK, et al. Self-reported long total sleep duration is associated with metabolic syndrome: the Guangzhou Biobank Cohort Study. Diabetes care. 2011;34(10):2317–9. Epub 2011/08/30. pmid:21873559; PubMed Central PMCID: PMC3177714.
- 28. Chaput JP, Despres JP, Bouchard C, Astrup A, Tremblay A. Sleep duration as a risk factor for the development of type 2 diabetes or impaired glucose tolerance: analyses of the Quebec Family Study. Sleep Med. 2009;10(8):919–24. Epub 2009/04/01. pmid:19332380.
- 29. Kim CW, Yun KE, Jung HS, Chang Y, Choi ES, Kwon MJ, et al. Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses. Journal of hepatology. 2013;59(2):351–7. pmid:23578884.
- 30. Miyake T, Kumagi T, Furukawa S, Hirooka M, Kawasaki K, Koizumi M, et al. Short sleep duration reduces the risk of nonalcoholic fatty liver disease onset in men: a community-based longitudinal cohort study. J Gastroenterol. 2015;50(5):583–9. pmid:25120172.
- 31. Chou YT, Cheng HJ, Wu JS, Yang YC, Chou CY, Chang CJ, et al. The association of sleep duration and sleep quality with non-alcoholic fatty liver disease in a Taiwanese population. Obesity research & clinical practice. 2018;12(6):500–5. Epub 2018/06/23. pmid:29929928.
- 32. Medic G, Wille M, Hemels ME. Short- and long-term health consequences of sleep disruption. Nature and science of sleep. 2017;9:151–61. Epub 2017/06/06. pmid:28579842; PubMed Central PMCID: PMC5449130.
- 33. Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. The Journal of clinical endocrinology and metabolism. 2009;94(8):2692–701. Epub 2009/05/28. pmid:19470627.
- 34. Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Current pharmaceutical design. 2005;11(32):4145–51. Epub 2005/12/27. pmid:16375736.
- 35. Seetho IW, Parker RJ, Craig S, Duffy N, Hardy KJ, Wilding JP, et al. Serum urate and obstructive sleep apnoea in severe obesity. Chron Respir Dis. 2015;12(3):238–46. Epub 2015/05/21. pmid:25990129.
- 36. Mirrakhimov AE, Mirrakhimov EM. Obstructive sleep apnoea, gout and cardiovascular risk: a worth studying association. Med Hypotheses. 2013;81(4):749. Epub 2013/08/14. pmid:23937998.
- 37. Wan YF, Zheng YL, Niu HY, Xu CQ, He YQ, Wang Y, et al. Uric acid levels in obstructive sleep apnea patients with atrial fibrillation. Archives of medical research. 2014;45(2):132–7. Epub 2013/12/10. pmid:24316394.
- 38. Abrams B. High prevalence of gout with sleep apnea. Med Hypotheses. 2012;78(2):349. Epub 2011/11/22. pmid:22098723.
- 39. Zhao K, Luan X, Liu Z, Zhu Z, Chen H, Shen H, et al. Low serum uric acid levels in chronic insomnia patients: A case-control study. Neurosci Lett. 2017;657:102–5. Epub 2017/08/13. pmid:28801272.
- 40. He W, Qiu H, Zhu J, Feng W, Lin Y, Shu M, et al. The effect of uric acid on sleep quality after acute ischemic stroke. Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia. 2019. Epub 2019/08/20. pmid:31420274.
- 41. Papandreou C, Babio N, Diaz-Lopez A, Martinez-Gonzalez MA, Becerra-Tomas N, Corella D, et al. Sleep Duration is Inversely Associated with Serum Uric Acid Concentrations and Uric Acid to Creatinine Ratio in an Elderly Mediterranean Population at High Cardiovascular Risk. Nutrients. 2019;11(4). Epub 2019/04/04. pmid:30939748; PubMed Central PMCID: PMC6521014.
- 42. Kanagasabai T, Ardern CI. Contribution of Inflammation, Oxidative Stress, and Antioxidants to the Relationship between Sleep Duration and Cardiometabolic Health. Sleep. 2015;38(12):1905–12. Epub 2015/08/04. pmid:26237775; PubMed Central PMCID: PMC4667380.
- 43. Cui L, Meng L, Wang G, Yuan X, Li Z, Mu R, et al. Prevalence and risk factors of hyperuricemia: results of the Kailuan cohort study. Modern rheumatology. 2017;27(6):1066–71. Epub 2017/04/12. pmid:28395604.
- 44. Wiener RC, Shankar A. Association between Serum Uric Acid Levels and Sleep Variables: Results from the National Health and Nutrition Survey 2005–2008. International journal of inflammation. 2012;2012:363054. Epub 2012/09/13. pmid:22970407; PubMed Central PMCID: PMC3434384.
- 45. Tsai PS, Wang SY, Wang MY, Su CT, Yang TT, Huang CJ, et al. Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects. Quality of life research: an international journal of quality of life aspects of treatment, care and rehabilitation. 2005;14(8):1943–52. Epub 2005/09/13. pmid:16155782.
- 46. Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med. 2015;11(6):591–2. Epub 2015/05/17. pmid:25979105; PubMed Central PMCID: PMC4442216.
- 47. Chu NF. Prevalence of obesity in Taiwan. Obesity reviews: an official journal of the International Association for the Study of Obesity. 2005;6(4):271–4. Epub 2005/10/26. pmid:16246212.
- 48. National High Blood Pressure Education P. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2004.
- 49. Diagnosis and classification of diabetes mellitus. Diabetes care. 2014;37 Suppl 1:S81–90. Epub 2013/12/21. pmid:24357215.
- 50. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Annals of internal medicine. 2009;150(9):604–12. Epub 2009/05/06. pmid:19414839; PubMed Central PMCID: PMC2763564.
- 51. Kanagasabai T, Ardern CI. Inflammation, Oxidative Stress, and Antioxidants Contribute to Selected Sleep Quality and Cardiometabolic Health Relationships: A Cross-Sectional Study. Mediators Inflamm. 2015;2015:824589. Epub 2015/11/17. pmid:26568665; PubMed Central PMCID: PMC4629050.
- 52. Fabbrini E, Serafini M, Colic Baric I, Hazen SL, Klein S. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects. Diabetes. 2014;63(3):976–81. Epub 2013/12/20. pmid:24353177; PubMed Central PMCID: PMC3931399.
- 53. Bowman GL, Shannon J, Frei B, Kaye JA, Quinn JF. Uric acid as a CNS antioxidant. Journal of Alzheimer's disease: JAD. 2010;19(4):1331–6. Epub 2010/01/12. pmid:20061611; PubMed Central PMCID: PMC2859185.
- 54. Ok EJ, Kim K, Park SB. Association between Serum Uric Acid and Oxidative Stress in Korean Adults. Korean journal of family medicine. 2018;39(5):295–9. Epub 2018/09/11. pmid:30196649; PubMed Central PMCID: PMC6166115.
- 55. Hill VM, O'Connor RM, Sissoko GB, Irobunda IS, Leong S, Canman JC, et al. A bidirectional relationship between sleep and oxidative stress in Drosophila. PLoS biology. 2018;16(7):e2005206. Epub 2018/07/13. pmid:30001323; PubMed Central PMCID: PMC6042693.
- 56. Villafuerte G, Miguel-Puga A, Rodriguez EM, Machado S, Manjarrez E, Arias-Carrion O. Sleep deprivation and oxidative stress in animal models: a systematic review. Oxidative medicine and cellular longevity. 2015;2015:234952. Epub 2015/05/07. pmid:25945148; PubMed Central PMCID: PMC4402503.
- 57. Kang DH, Ha SK. Uric Acid Puzzle: Dual Role as Anti-oxidantand Pro-oxidant. Electrolyte & blood pressure: E & BP. 2014;12(1):1–6. Epub 2014/07/26. pmid:25061467; PubMed Central PMCID: PMC4105384.
- 58. Liu W, Zhang R, Tan A, Ye B, Zhang X, Wang Y, et al. Long sleep duration predicts a higher risk of obesity in adults: a meta-analysis of prospective cohort studies. Journal of public health (Oxford, England). 2019;41(2):e158–e68. Epub 2018/08/15. pmid:30107483.
- 59. Patel SR, Hu FB. Short sleep duration and weight gain: a systematic review. Obesity (Silver Spring, Md). 2008;16(3):643–53. Epub 2008/02/02. pmid:18239586; PubMed Central PMCID: PMC2723045.
- 60. Kim CE, Shin S, Lee HW, Lim J, Lee JK, Shin A, et al. Association between sleep duration and metabolic syndrome: a cross-sectional study. BMC public health. 2018;18(1):720. Epub 2018/06/14. pmid:29895272; PubMed Central PMCID: PMC5998453.
- 61. Irwin M, Thompson J, Miller C, Gillin JC, Ziegler M. Effects of sleep and sleep deprivation on catecholamine and interleukin-2 levels in humans: clinical implications. The Journal of clinical endocrinology and metabolism. 1999;84(6):1979–85. Epub 1999/06/18. pmid:10372697.
- 62. Beyl RN Jr., Hughes L, Morgan S. Update on Importance of Diet in Gout. The American journal of medicine. 2016;129(11):1153–8. Epub 2016/10/25. pmid:27452679.
- 63. Saag KG, Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis research & therapy. 2006;8 Suppl 1:S2. Epub 2006/07/06. pmid:16820041; PubMed Central PMCID: PMC3226107.
- 64. Qiu L, Cheng XQ, Wu J, Liu JT, Xu T, Ding HT, et al. Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces. BMC public health. 2013;13:664. Epub 2013/07/20. pmid:23866159; PubMed Central PMCID: PMC3722003.
- 65. Ali N, Rahman S, Islam S, Haque T, Molla NH, Sumon AH, et al. The relationship between serum uric acid and lipid profile in Bangladeshi adults. BMC cardiovascular disorders. 2019;19(1):42. Epub 2019/02/23. pmid:30791868; PubMed Central PMCID: PMC6385393.
- 66. Peng TC, Wang CC, Kao TW, Chan JY, Yang YH, Chang YW, et al. Relationship between hyperuricemia and lipid profiles in US adults. Biomed Res Int. 2015;2015:127596. Epub 2015/01/30. pmid:25629033; PubMed Central PMCID: PMC4299312.
- 67. Tanaka K, Ogata S, Tanaka H, Omura K, Honda C, Hayakawa K. The relationship between body mass index and uric acid: a study on Japanese adult twins. Environmental health and preventive medicine. 2015;20(5):347–53. Epub 2015/06/04. pmid:26037073; PubMed Central PMCID: PMC4550610.
- 68. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes. 2002;51(12):3391–9. Epub 2002/11/28. pmid:12453891.
- 69. Borst SE. The role of TNF-alpha in insulin resistance. Endocrine. 2004;23(2–3):177–82. Epub 2004/05/18. pmid:15146098.
- 70. Gee Teng G, Pan A, Yuan JM, Koh WP. Cigarette Smoking and the Risk of Incident Gout in a Prospective Cohort Study. Arthritis care & research. 2016;68(8):1135–42. Epub 2015/12/30. pmid:26714165; PubMed Central PMCID: PMC5515666.
- 71. Wang W, Krishnan E. Cigarette smoking is associated with a reduction in the risk of incident gout: results from the Framingham Heart Study original cohort. Rheumatology (Oxford). 2015;54(1):91–5. Epub 2014/08/03. pmid:25086327.
- 72. Bandaru P, Shankar A. Association between Serum Uric Acid Levels and Diabetes Mellitus. International journal of endocrinology. 2011;2011:604715. Epub 2011/11/25. pmid:22114591; PubMed Central PMCID: PMC3216382.
- 73. Chiou WK, Wang MH, Huang DH, Chiu HT, Lee YJ, Lin JD. The relationship between serum uric acid level and metabolic syndrome: differences by sex and age in Taiwanese. Journal of epidemiology. 2010;20(3):219–24. Epub 2010/03/24. pmid:20308795; PubMed Central PMCID: PMC3900844.
- 74. Chang HC, Yang HC, Chang HY, Yeh CJ, Chen HH, Huang KC, et al. Morbid obesity in Taiwan: Prevalence, trends, associated social demographics, and lifestyle factors. PLoS One. 2017;12(2):e0169577. Epub 2017/02/06. pmid:28152059; PubMed Central PMCID: PMC5289420.
- 75. Pan Z, Huang M, Fang M, Xie X, Huang Z. Socioeconomic differences in hyperuricemia and gout: a systematic review and meta-analysis. Endocrine. 2020. Epub 2020/04/15. pmid:32285287.